title: Frequency of abnormal human haemoglobins caused by C----T transitions in CpG dinucleotides.
abstract: A large part of human genetic disease apparently arises from deamination of cytosines in methylated CpG dinucleotides. Their mutation rate is known to be high when C is present as 5-methylcytosine, but is believed to be normal when it is unmethylated. The beta-globin gene contains five, the gamma-globin gene two, and each of the alpha-globin genes contain 35 CpGs. The CpGs in the beta- and gamma-globin genes are methylated, while those in the alpha-globin genes are undermethylated. One would therefore have expected the CpGs to be a frequent source of mutations in the beta- and gamma-globin genes, but not in the alpha-globin genes. In fact, the evidence points to CpGs being a frequent source of mutations in both the alpha- and beta-globin genes. This suggests either that the mutation rates of both methylated and unmethylated CpGs are abnormally high, which conflicts with published evidence, or that there is a finite chance of some CpGs in the alpha-globin genes of certain individuals being methylated and therefore subject to mutation.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, U.K.
authors.forename: M F
authors.initials: MF
authors.lastname: Perutz
mesh_terms: D001483:Base Sequence; D003062:Codon / Q000235:genetics; D003596:Cytosine; D015226:Dinucleoside Phosphates / Q000235:genetics*; D005914:Globins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D013941:Thymine
chemical_list: D003062:Codon; D003596:Cytosine; D015226:Dinucleoside Phosphates; D005914:Globins; D006455:Hemoglobins, Abnormal; D012333:RNA, Messenger; D013941:Thymine; C015772:CpG dinucleotide